The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index; 13 of the 16 sources its claims cite were checked for support.
Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer’s disease
Open accessAbstract
Microglia play a critical role in brain homeostasis and disease progression. In neurodegenerative conditions, microglia acquire the neurodegenerative phenotype (MGnD), whose function is poorly understood. MicroRNA-155 (miR-155), enriched in immune cells, critically regulates MGnD. However, its role in Alzheimer's disease (AD) pathogenesis remains unclear. Here, we report that microglial deletion of miR-155 induces a pre-MGnD activation state via interferon-γ (IFN-γ) signaling, and blocking IFN-γ signaling attenuates MGnD induction and microglial phagocytosis. Single-cell RNA-sequencing analysis of microglia from an AD mouse model identifies Stat1 and Clec2d as pre-MGnD markers. This phenotypic transition enhances amyloid plaque compaction, reduces dystrophic neurites, attenuates plaque-associated synaptic degradation and improves cognition. Our study demonstrates a miR-155-mediated regulatory mechanism of MGnD and the beneficial role of IFN-γ-responsive pre-MGnD in restricting neurodegenerative pathology and preserving cognitive function in an AD mouse model, highlighting miR-155 and IFN-γ as potential therapeutic targets for AD.
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Claims the paper makes
92 Own result · 24 Own method · 22 Own interpretation · 4 Supported · 2 Partly supported · 2 Couldn’t confirm · 2 Sources not found · 1 No full text of the sources · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Detailed analysis of the pre-MGnD cluster revealed two IFN-responsive early-and late-pre-MGnD clusters showing upregulation of genes including Stat1, Isg15, Ifi204, Irf7, Ifit1, and Ifit3, which strongly resembled the previously determined Interferon Response Microglia (IRM) 35 (Fig. 2e,f and Extended Data Fig. 6k,l).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation primes microglia to pre-MGnD via IFNγ
What the sources say
- Supportedcites [35] Sala Frigerio, C. et al. The major risk factors for Alzheimer’s disease: age, sex, and genes modulate the microglia response to Aβ plaques. Cell Rep. 27, 1293–1306 (2019). source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Moreover, C-Type Lectin-Receptor-2d (Clec2d), which has been shown to recognize histones released upon necrotic cell death and to mediate inflammation 36 , was enriched in both early and late pre-MGnD clusters.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation primes microglia to pre-MGnD via IFNγ
What the sources say
- Supportedcites [36] Lai, J. J., Cruz, F. M. & Rock, K. L. Immune sensing of cell death through recognition of histone sequences by C-type lectin-receptor-2d causes inflammation and tissue injury. Immunity 52, 123–135 (2020). source
The citation supports the background clause about Clec2d, not the citing authors’ observation about pre-MGnD clusters. The source’s Results identify histones as Clec2d ligands, and its Discussion says Clec2d senses histones exposed or released during cell death and contributes to inflammatory responses and tissue damage. No page numbers were provided in our copy. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Shared DEGs from both datasets were associated with enhanced IFN signaling, indicating the IFN pathway as an early response in microglia reacting to remote pathological changes 7,34 (Fig 1h,i).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Targeting microglial miR-155 enhances the MGnD phenotype
What the sources say
- Partly supportedcites [7] Krasemann, S. et al. The TREM2–APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581 (2017). sourceExperimental — accuracy not yet measured
The Results section on the MGnD subset identifies Clec7a+ microglia associated with plaques in APP-PS1 mice, and the Discussion notes some overlap between the MGnD phenotype and an IFNγ-induced phenotype (page numbers unavailable). But our copy does not report shared DEGs between the specified APP-PS1 and APP-PS1:miR-155 cKO comparisons or show that those DEGs are associated with enhanced IFN signaling. (LLM, conf=0.78)
- Partly supportedcites [34] Roy, E. R. et al. Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease. J. Clin. Invest. 130, 1912–1930 (2020). sourceExperimental — accuracy not yet measured
In “Prevalent IFN pathway activation in Aβ models and amyloid-induced IFN response” (Figure 4B; page unavailable), the paper reports upregulated IFN-pathway genes in Clec7a+ microglia from APP-PS1 mice. It does not report the APP/PS1:miR-155 cKO comparison or identify DEGs shared between the two datasets, so it cannot establish the claimed shared-gene result. Its principal finding concerns plaque-associated microglia, not an early response to remote pathology. (LLM, conf=0.86)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, the pre-MGnD cluster size was expanded in APP/PS1:miR-155 cKO compared to APP/PS1 mice (Extended Data Figs.6f,o)”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation primes microglia to pre-MGnD via IFNγ
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Gene set enrichment analysis (GSEA), gene ontology (GO) enrichment analysis, and IPA canonical pathway analysis showed that IFN signaling pathway was enhanced in APP/PS1:miR-155 cKO microglia (Fig. 1j and Extended Data Fig. 5a,b).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Targeting microglial miR-155 enhances the MGnD phenotype
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We validated these findings by immunohistochemistry of synaptic molecules and found significantly more synapses preserved in cortical peri-plaque regions in 8-month-old APP/PS1:miR-155 cKO mice as compared to APP/PS1 mice (Fig. 5e,f).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Enhanced synaptic preservation in APP/PS1:miR-155 cKO mice
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that homeostatic microglia progressed towards mature MGnD via the early and late pre-MGnD clusters, in both sexes (Fig. 2g and Extended Data Fig. 6m).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation primes microglia to pre-MGnD via IFNγ
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We next analyzed microglia from 8-month-old mice using SmartSeq2 RNAseq and found less DEGs affected in APP/PS1:miR-155 cKO mice as compared to 4-month-old mice (Extended Data Fig. 2b and Supplementary Table 1).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Targeting microglial miR-155 enhances the MGnD phenotype
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed a significant increase in the sphericity of Thioflavin-S + compact plaques in APP/PS1:miR-155 cKO mice at both 4 and 8 months of age (Fig. 4h).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 deficient microglia restrict Aβ pathology
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We masked ApoE signal in non-plaque region and found a trend towards increased number of co-localized ApoE + /Thioflavin-S + voxels in plaques at 4 months (P = 0.05) (Fig. 4j).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 deficient microglia restrict Aβ pathology
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 38
- Probably not a substantial claim. 46
Every source the paper cites for this claim was checked and supports it.
In the paper
“miR-155 is conserved between mice and humans, suggesting its conserved gene regulatory function 24 .”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Discussion
What the sources say
- Supportedcites [24] Faraoni, I., Antonetti, F. R., Cardone, J. & Bonmassar, E. miR-155 gene: a typical multifunctional microRNA. Biochim. Biophys. Acta 1792, 497–505 (2009). source
Section 2 (page unavailable) says miR-155 is processed from BIC, which has strong sequence homology among humans, mice and chickens, implying an evolutionarily conserved function. The Introduction (page unavailable) describes microRNAs as regulators of gene expression, supporting the claim’s gene-regulatory framing. (LLM, conf=0.87)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Our sample sizes for experiments were chosen based on our prior publication using APP/PS1 mice 58 , which defined the expectations for the effect size and variance 55 .”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Statistical analysis
What the sources say
- Could not verifycites [58] Zappia, L. & Oshlack, A. Clustering trees: a visualization for evaluating clusterings at multiple resolutions. Gigascience 7, giy083 (2018). sourceExperimental — accuracy not yet measured
The cited paper’s Methods > Simulations section describes statistical distributions used to generate clustering datasets, not effect-size or variance expectations for APP/PS1 mouse experiments. Searches for APP/PS1 mice, experimental sample sizes, and effect size and variance found no passage addressing the claim. Page numbers were not provided in our copy. (LLM, conf=0.75)
- Could not verifycites [55] Garcia-Alonso, L., Holland, C. H., Ibrahim, M. M., Turei, D. & Saez-Rodriguez, J. Benchmark and integration of resources for the estimation of human transcription factor activities. Genome Res. 29, 1363–1375 (2019). sourceExperimental — accuracy not yet measured
The Methods (Benchmark data; page unavailable) describe transcription-factor perturbation experiments in human cell lines, not APP/PS1 mouse experiments. Searches for APP/PS1 mice, effect size, variance, and sample-size planning found no passage showing that this paper defined the expectations cited as reference 55. The mouse study is separately cited as reference 58. (LLM, conf=0.76)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Potential dublets were detected using scDblFinder (v1.12.0) 62 and filtered out.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Single-cell processing and analysis
What the sources say
- Could not verifycites [62] Mantri, M. et al. Spatiotemporal single-cell RNA sequencing of developing chicken hearts identifies interplay between cellular differentiation and morphogenesis. Nat. Commun. 12, 1771 (2021). sourceExperimental — accuracy not yet measured
The Methods section on scRNA-seq data processing (page unavailable) describes excluding cells based on gene counts and mitochondrial transcripts, but does not mention doublet detection or removal. Searches for scDblFinder, doublet detection, and v1.12.0 found no supporting passage in our copy. (LLM, conf=0.76)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“Additionally, increased miR-155 expression has been observed in mouse models of AD and in hippocampal tissue from AD donors 28,47 .”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Discussion
What the sources say
- Supportedcites [28] Readhead, B. et al. miR-155 regulation of behavior, neuropathology, and cortical transcriptomics in Alzheimer’s disease. Acta Neuropathol. 140, 295–315 (2020). source
The Results section reports elevated miR155 in the hippocampus of APP/PSEN1 mice and significantly higher miR155 signal in postmortem CA1 hippocampal tissue from AD subjects than from controls. The Discussion also reports elevated miR155 in 12-month-old APP/PSEN1 mice. (LLM, conf=0.94)
- Supportedcites [47] Sierksma, A. et al. Deregulation of neuronal miRNAs induced by amyloid-β or TAU pathology. Mol. Neurodegener. 13, 54 (2018). source
The Results section (‘Confirmation of changes in a separate cohort of APPtg mice and in AD patients’) reports increased hsa-miR-155-5p expression in hippocampal tissue from AD patients compared with non-demented controls. It also concludes that miR-155-5p is upregulated in the studied mouse models of neurodegeneration, including the APPtg model of AD. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Other previous studies have shown no differential expression of miR-155 in AD brains [48][49][50] .”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Discussion
What the sources say
- Supportedcites [48] Culpan, D., Kehoe, P. G. & Love, S. Tumour necrosis factor-α (TNF-α) and miRNA expression in frontal and temporal neocortex in Alzheimer’s disease and the effect of TNF-α on miRNA expression in vitro. Int. J. Mol. Epidemiol. Genet. 2, 156–162 (2011).
Table 1 reports miR-155 expression as not significantly different between AD and control brains in both frontal and temporal neocortex (p. 159). This supports the claim of no detected differential expression in the brain regions studied. (LLM, conf=0.94)
- Could not verifycites [49] Patrick, E. et al. Dissecting the role of non-coding RNAs in the accumulation of amyloid and tau neuropathologies in Alzheimer’s disease. Mol. Neurodegener. 12, 51 (2017). sourceExperimental — accuracy not yet measured
The Results section on miRNAs associated with pathologic AD identifies two significant miRNAs, but does not report a result for miR-155. Searches for miR-155 and variant wording found no passage establishing whether it was tested or differentially expressed in AD brains. (LLM, conf=0.76)
- Could not verifycites [50] Lau, P. et al. Alteration of the microRNA network during the progression of Alzheimer’s disease. EMBO Mol. Med. 5, 1613–1634 (2013). sourceExperimental — accuracy not yet measured
The Results sections report differentially expressed miRNAs in AD brain samples, but the passages found do not report a result for miR-155 or establish whether it was tested. Searches for “miR-155” and its differential expression found no passage that settles the claim. (LLM, conf=0.68)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The MGnD cluster was strongly enriched in MGnD genes including Clec7a, Apoe, Trem2 as compared to the M0, early and late IFN-responsive pre-MGnD clusters, but significantly reduced the expression of Clec2d and IFN-responsive genes (Fig. 2f, Extended Data Fig. 6l, and Supplementary Table 2).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation primes microglia to pre-MGnD via IFNγ
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The pre-MGnD cluster was defined by the intermediate expression of both Tmem119 and Clec7a.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation primes microglia to pre-MGnD via IFNγ
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the overlap of DEGs was minimal involving only 9 genes, none of which were canonical MGnD genes (Extended Data Fig. 2d).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Targeting microglial miR-155 enhances the MGnD phenotype
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, APP/PS1:miR-155 cKO mice exhibited a preference for the novel arm over the familiar arms, confirming restoration of functional recognition memory.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation rescues behavioral deficits in APP/PS1 mice
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found enhanced phagocytosis of Aβ by Clec7a + microglia in 4-month-old APP/PS1:miR-155 cKO mice compared to controls (Fig. 4a,f), which was not detected in 8-month-old mice (Fig. 4f).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 deficient microglia restrict Aβ pathology
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, the early pre-MGnD cluster retained a high expression of M0 genes and low expression of MGnD genes (Fig. 2f and Extended Data Fig. 6l), whereas the late pre-MGnD cluster preferentially expressed several MGnD genes including Clec7a, Apoe, and Axl, and had reduced expression of homeostatic microglial genes.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation primes microglia to pre-MGnD via IFNγ
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed a significant reduction in 6E10 + Aβ plaque number and area in APP/PS1:miR-155 cKO brains at 4 months (Extended Data Fig. 9a,b), but not at 8 months (Extended Data Fig. 9c).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 deficient microglia restrict Aβ pathology
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“APP/PS1 mice at 8 months of age showed reduced spontaneous alternation (SA) compared to non-transgenic mice in the Y-maze task (Fig. 6a,c), indicating an impairment in visuospatial working memory.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation rescues behavioral deficits in APP/PS1 mice
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“APP/PS1 mice at 8 months of age did not demonstrate a significant preference to enter the novel arm, indicating an impairment in recognition memory (Fig. 6b,d).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation rescues behavioral deficits in APP/PS1 mice
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, qPCR analysis showed a significant upregulation of Clec2d and downregulation of P2ry12 in the early-and late-pre-MGnD clusters (Extended Data Fig. 7f).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation primes microglia to pre-MGnD via IFNγ
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, deletion of microglial miR-155 upregulated the expression of MGnD genes, such as Clec7a, Tyrobp and Lpl, and suppressed the level of homeostatic genes, such as Tmem119, in the proliferating microglia clusters (Clusters 8 and 9, Extended Data Fig. 6e).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation primes microglia to pre-MGnD via IFNγ
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, APP/PS1:miR-155 cKO mice showed rescued performance in the SA task, and miR-155 cKO had no effect in nontransgenic mice.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation rescues behavioral deficits in APP/PS1 mice
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“miR-155 was highly expressed in microglia from APP/PS1 mice at 4 and 8 months of age, but significantly reduced in APP/PS1:miR-155 cKO (Fig. 1b and Extended Data Fig. 2a).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Targeting microglial miR-155 enhances the MGnD phenotype
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Quantification of % correct spontaneous alternations in the Y-maze SA for 8-month-old WT and APP/PS1 mice with and without microglia specific miR-155 ablation.Two-way ANOVA with Tukey's post hoc test, APP/PS1 vs. APP/PS1:miR-155 cKO, P = 0.004 (n = 34 WT, n = 36 miR-155 cKO, n = 35 APP/PS1 and n = 30 APP/ PS1:miR-155 cKO mice).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Quantification of % 6E10/Celc7a volume at 4 (P = 0.0007 by two-tailed Students unpaired t-test test) and 8 months of age (P = 0.6876 by two-tailed Student's unpaired t-test), n = 6 mice per group.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plainn = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Center zone time for WT and APP/PS1 mice.There were no statistically significant differences between any groups by two-way ANOVA with Bonferoni's post hoc test (n = 34 WT, n = 37 miR-155 cKO, n = 35 APP/PS1 and n = 29 APP/PS1:miR-155 cKO mice).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Statistical analysis
plainn = 34- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“qPCR of miR-155 expression of 4-month-old mice showing the efficiency of tamoxifen treatment using one-way ANOVA, P < 0.0001 by one-way ANOVA with Tukey's post hoc test (n = 6 mice for miR-155 cKO group; n = 3 mice for the other three groups).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plainn = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“entries into the familiar arms was compared for each mouse by repeated measure three-way ANOVA with Bonferoni's post hoc test, WT P = 0.0002, miR-155 cKO P= 0.0064, APP/PS1 P = 0.2361, APP/PS1:miR-155 cKO P = 0.0212 (n = 34 WT, n = 36 miR-155 cKO, n = 35 APP/PS1 and n = 30 APP/PS1:miR-155 cKO mice).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Statistical analysis
plainn = 30- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“6E10 plaque counts normalized to area and percent area 6E10 positivity in 4-month-old mice.P Values were determined using two-tailed Student's unpaired t-test, P = 0.0084 and P = 0.0104, respectively (n = 10 APP/PS1, n = 9 APP/PS1:miR-155 cKO).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plaincorrelationaln = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Volcano plots of DEPs between APP/PS1:miR-155 cKO and APP/PS1 whole brain tissue, P < 0.05 using two-sided Wald test.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“59 and 160 pre-MGnD markers were identified in females and males, respectively.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Single-cell processing and analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Violin plots showing the mean Z-score of pre-MGnD markers in APP/PS1 and APP/PS1:miR-155 cKO male mice.P = 3.54507e-91 by Kruska-Wallis test, FDR corrected using Benjamini Hochberg.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Total distance traveled over time in the open field locomotor activity task.Main effect of APP transgene by two-way ANOVA, WT vs. APP/PS1, P < 0.0001; APP/PS1 and APP/PS1:miR-155 cKO are not statistically different by two-way ANOVA with Bonferoni's post hoc test (n = 34 WT, n = 37 miR-155 cKO, n = 35 APP/PS1 and n = 29 APP/PS1:miR-155 cKO mice).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Statistical analysis
plainn = 29- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The method returned 16 cell clusters for females and 20 clusters for males which were then visualized using UMAP for dimensionality reduction.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Single-cell processing and analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Heatmap of DEGs identified in APP/PS1:miR-155 cKO microglia, compared to APP/PS1 microglia using DESeq2 analysis.FDR-corrected P < 0.05, sex-specific DEGs removed (n = 4-6 mice per sex/group).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plainn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Quantification of the percentage of colocalized area of Vglut2/Psd95 in the plaque and peri-plaque regions of 8-month-old mice compared using two-tailed Mann-Whitney test, P = 0.0275, 36 plaques from APP/PS1 (n = 6) mice and 29 plaques from APP/PS1:miR-155 cKO (n = 5) mice.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plainn = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Quantification of percentage of four clusters mentioned in d from WT, 2-and 8-month-old APP/PS1 mice, P < 0.0001 for M0 and late pre-MGnD, P = 0.0011 (WT vs. 8-month-old APP/PS1) and P = 0.0084 (2-month-old APP/PS1 vs. 8-month-old APP/PS1) for early pre-MGnD, P = 0.0017 (WT vs. 8-month-old APP/PS1) and P = 0.0014 (2-month-old APP/PS1 vs. 8-month-old APP/PS1) for MGnD as determined by one-way ANOVA”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plaincorrelationaln = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Heatmap of DEGs identified in miR-155 cKO microglia, compared to WT microglia for male (c) and female (d) groups using DESeq2 analysis, two-sided Wald test, FDR-corrected P < 0.05 (n = 5-6 mice per sex group).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plainn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Heatmap of DEG in phagocytic and non-phagocytic microglia isolated from WT and Ifngr1 cKO mice using DESeq2 analysis.Two-sided LRT statistical test with an FDRcorrected P < 0.05, n = 3 mice per group.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Violin plots showing the mean Z-score of pre-MGnD markers in all the cells from APP/PS1 and APP/PS1:miR-155 cKO mice; P = 6.829469e-12 by Kruskal-Wallis test, FDR corrected using Benjamini Hochberg.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Heatmaps of significantly changed proteins between male APP/PS1:miR-155 cKO and APP/PS1 whole brain tissue at 4 and 8 months of age (one-way ANOVA with Student's t-test between APP/PS1 and APP/PS1:miR-155 cKO mice, P < 0.05, n = 3-4 male mice per group).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fold changes of luciferase activity after non-mutated Stat1 3'UTR co-transfected with the non-relevant miRNA mimic (miR-18), P = 0.0072 by one-way ANOVA with post hoc Tukey's test (n = 3).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Validation of Stat1 and Clec2d pre-MGnD markers.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plainn = 12- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After filtering all databases for high-confidence targets, 1680 potential target genes were selected.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Targetome analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Decreased 6E10 + amyloid plaque burden and enhanced phagocytosis function in APP/PS1:miR-155 cKO mice.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plaindirectn = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Bar graphs depicting expression levels of select genes from (a) using two-way ANOVA with Holm-Sidak post hoc analysis, P = 0.042 for Lpl, P = 0.0331 for Spp1, P = 0.0031 for Egr1, P = 0.0018 for Cst3 and Mertk (n = 3 mice).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Quantification of Tmem119 positive area/plaque in 4-month-old (P = 0.0063 by two-tailed Student's unpaired t-test) and 8-month-old mice (P = 0.5687 by two-tailed Student's unpaired t-test), n = 6 mice per group.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plainn = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data demonstrate that miR-155 ablation expands the number of microglia in the pre-MGnD cluster and augments the immune pathway enrichment within this cluster.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation primes microglia to pre-MGnD via IFNγ
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we demonstrate that microglial-specific deletion of miR-155 potentiates the transition from homeostatic to pre-MGnD microglia and enhances microglial immune functions within the pre-MGnD cluster.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, our study suggests that pre-MGnD microglia serve as restrictors of plaque associated pathology, highlighting a therapeutically relevant role for this cluster in rescuing cognitive function.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, these data show that miR-155 deletion enhanced MGnD signature in APP/PS1:miR-155 cKO microglia and enriched IFN signaling and phagocytic pathways at 4 months of age.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Targeting microglial miR-155 enhances the MGnD phenotype
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, we found an important role of miR-155 in regulating IFNγ signaling which governs the transition from homeostatic to pre-MGnD and MGnD.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, these data demonstrate that microglia transition from homeostatic to MGnD via an IFN-responsive intermediate state, and that miR-155 ablation enhances the size and immune response features of this pre-MGnD state.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation primes microglia to pre-MGnD via IFNγ
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, these data demonstrate that there is a significant overlap in genes affected by miR-155 cKO and IFNγ manipulation, and that IFNγ blockade suppresses microglial phagocytosis and microglial response to MGnD induction in miR-155 cKO mice.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > IFNγ is regulated by miR-155 and induces pre-MGnD signature
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“miR-155 targets Stat1 and regulates interferon signaling pathway.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
plaindirectn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Sample viability and counts were determined using hemocytometer and trypan blue and ranged from [510,000-1,300,000 counts/ml] and [72-89% viability].”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Single-cell RNA sequencing
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Data for each experiment were collected and processed randomly and animals were assigned to various experimental groups randomly as well.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For all comparisons groups were assessed for normal distribution.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Enhancing the pre-MGnD cluster represents a potential immunomodulatory approach to treat AD.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“differentially expressed genes (DEGs) were identified by running comparisons using LRT where the cutoff for significant genes was a Benjamini-Hochberg FDR corrected P < 0.05.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Bulk RNA sequencing and analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Analysis of all images was done while blinded to mouse genotype.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Confocal analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“No data points were excluded from analysis.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Data collection and analysis were blindly performed.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“to obtain a protein identification FDR of less than 1%.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Mass spectrometry data processing and spectra assignment
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Total signal-to-noise values for all peptides were summed for each TMT channel and all values were adjusted to account for variance and a total minimum signal-to-noise value of 200 was implemented.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Determination of TMT reporter ion intensities
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Previous studies using both the spontaneous and forced alternation tasks have shown no risk of confound from using the same maze with sufficient time between trials 71 .”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Forced Alternation
What the sources say
- Not matchedcites [71]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“a previous study showed that miR-155 expression was highly specific to cells of hematopoietic origin 51 .”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Discussion
What the sources say
- Not checked — no full text of the sourcecites [51] Landgraf, P. et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129, 1401–1414 (2007). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“DEGs were identified using DESeq2 analysis with FDR-corrected P < 0.05 (n = 4-6 mice per group).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Statistical analysis
plainn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“DEGs between APP/PS1:miR-155 cKO and APP/PS1 were identified by running comparisons using LRT where the cutoff for significant genes was a Benjamini-Hochberg FDR corrected P < 0.05.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Single-cell processing and analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cells with more than 1000 sequencing reads and less than 20 percent mitochondrial transcripts were selected.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Single-cell processing and analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Clusters containing low-quality cells (high ribosome to mitochondria ratio), non-microglia cells and proliferating cells were removed for downstream analysis.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Single-cell processing and analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All behavioral testing was performed in a blinded manner.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Behavioral Tests
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Only genes present in more than 3 cells were included.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Single-cell processing and analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“using identical exposure times across samples for each fluorophore”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Epifluorescent image capturing
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Data were obtained from one independent experiment.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“While we could not detect miR-155 expression in CD206 + CAM using miRNAscope in aged APP/PS1 mice, we cannot fully rule out the possibility that miR-155 genetic disruption in CAM/BAM might contribute to the transcriptomic changes observed in microglia.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Cx3cr1 CreERT2-mediated deletion of miR-155 in non-microglial Cx3cr1+ cells (CAM/BAM) does not contribute to the transcriptomic changes observed in microglia.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Low abundance genes below a mean count of 5 reads/sample were filtered out”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Bulk RNA sequencing and analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All qRT-PCRs were performed in duplicate”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > RNA isolation and Quantitative Real-Time PCR
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, we show that miR-155 ablation enhances microglia transition from homeostatic to pre-MGnD and that the pre-MGnD phenotype is therapeutically relevant for restricting Aβ pathology.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“An MS2 spectra assignment false discovery rate (FDR) of less than 1% was implemented by applying the target-decoy database search strategy.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Mass spectrometry data processing and spectra assignment
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“First, we were limited in the number of timepoints for the scRNAseq of isolated myeloid cells.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Cx3cr1 CreERT2-mediated deletion of miR-155 in non-microglial Cx3cr1+ cells (CAM/BAM) does not contribute to the transcriptomic changes observed in microglia.
“we cannot fully rule out the possibility that miR-155 genetic disruption in CAM/BAM might contribute to the transcriptomic changes observed in microglia.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Importantly, ITGB8 blockade resulted in an increased IFNγ response, which we recently showed to play a critical role in the acquisition of beneficial pre-MGnD in AD mice 60 .”
From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [60]
The cited source says what the claim attributes to it.
In the citing paper
“Recently it was reported that conditional knockout of microRNA miR155 in microglia in APP/PS1 mice leads to activation of interferon-mediated signalling, which was associated with increased phagocytosis and plaque compaction (Yin et al, 2023a).”
From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Yin et al, 2023a
In the citing paper
“Stage-1 DAM represents a transitory and functional subtype with a higher capacity of phagocytosis initiated by a TREM2-independent mechanism, whereas stage-2 DAM represents a dysfunctional state that contributes to AD pathology initiated by a TREM2-dependent mechanism.99,111”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [111]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > miR-155 ablation primes microglia to pre-MGnD via IFNγ
“Unsupervised clustering revealed 17 clusters in the female dataset (Extended Data Fig. 6b).”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Single-cell processing and analysis
“The method returned 16 cell clusters for females and 20 clusters for males which were then visualized using UMAP for dimensionality reduction.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Plaque associated synaptic degradation
“6 individual plaques per animal were analyzed with 5-6 animals each group.”
§ Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease > Extended
“36 plaques from APP/PS1 (n = 6) mice and 29 plaques from APP/PS1:miR-155 cKO (n = 5) mice.”
Citations
Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Self-citationIntegrated analysis of multimodal single-cell data
Hao, Y., Hao, S., Andersen-Nissen, E., Mauck, W. M., Zheng, S., Butler, A., Lee, M. J., Wilk, A. J., Darby, C., Zagar, M., et al. (2020) · doi:10.1101/2020.10.12.335331 · Cited by 15,508
Fast, sensitive and accurate integration of single-cell data with Harmony
Korsunsky, I., Millard, N., Fan, J., Slowikowski, K., Zhang, F., Wei, K., Baglaenko, Y., Brenner, M., Loh, P.-R., & Raychaudhuri, S. (2019) · Nature Methods · doi:10.1038/s41592-019-0619-0 · Cited by 10,488
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197
Self-citationNeuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493
Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089
miRBase: microRNA sequences, targets and gene nomenclature
Griffiths-Jones, S. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj112 · Cited by 3,950
A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing
Landgraf, P., Rusu, M., Sheridan, R., Sewer, A., Iovino, N., Aravin, A., Pfeffer, S., Rice, A., Kamphorst, A. O., Landthaler, M., et al. (2007) · Cell · doi:10.1016/j.cell.2007.04.040 · Cited by 3,626
Cited by
Sorted by citations
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints
Yin, Z., Rosenzweig, N., Kleemann, K. L., Zhang, X., Brandão, W., Margeta, M. A., Schroeder, C., Sivanathan, K. N., Silveira, S., Gauthier, C., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01627-6 · Cited by 202
Self-citationMicroRNAs: pioneering regulators in Alzheimer’s disease pathogenesis, diagnosis, and therapy
Li, Y.-B., Fu, Q., Guo, M., Du, Y., Chen, Y., & Cheng, Y. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-03075-8 · Cited by 134
Self-citationNoteworthy perspectives on microglia in neuropsychiatric disorders
Zhu, H., Guan, A., Liu, J., Li, P., Zhang, Z., & Wang, S. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02901-y · Cited by 91
Rosenzweig, N., Kleemann, K. L., Rust, T., Carpenter, M., Grucci, M., Aronchik, M., Brouwer, N., Valenbreder, I., Cooper-Hohn, J., Iyer, M., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-03122-3 · Cited by 90
Self-citation
Metadata
- Authors
- Yin, Z., Herron, S., Silveira, S., Kleemann, K., Gauthier, C., Mallah, D., Cheng, Y., Margeta, M. A., Pitts, K. M., Barry, J.-L., Subramanian, A., Shorey, H., Brandao, W., Durao, A., Delpech, J.-C., Madore, C., Jedrychowski, M., Ajay, A. K., Murugaiyan, G., Hersh, S. W., Ikezu, S., Ikezu, T., & Butovsky, O.
- Affiliations
- Brigham and Women's Hospital (US)
- Boston University (US)
- Broad Institute (US)
- Harvard University (US)
- Corresponding author
- Ikezu, Tsuneya
- Butovsky, Oleg
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2023-06-08
- Volume
- 26
- Issue
- 7
- Pages
- 1196-1207
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC10619638
- OpenAlex
- W4379878477
- Cited by
- 120
- References
- 69
- Citations by year
- 2026: 36 · 2025: 32 · 2024: 42 · 2023: 10
- FWCI
- 13.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (R01AG054672, R01AG051812, R01AG075509, R21AG076982, R41AG073059, RF1AG054199, R01AG066429, R01AG072719, R01AG067763)
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (R01NS088137)
- U.S. Department of Health & Human Services | NIH | National Eye Institute (R01EY027921, K12 EY016335, K08 EY030160)
- BrightFocus Foundation (2020A016806)
- Cure Alzheimer’s Fund (APOE consortium)
- U.S. Department of Health & Human Services | National Institutes of Health (F31AG071106, T32GM008541)
- Research to Prevent Blindness Career Development Award.
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- microglia, Alzheimer's disease, miR-155, interferon-gamma signaling, STAT1, CLEC2D, dystrophic neurites, cognitive function, microglial phagocytosis, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Interferon-gamma, Mice, Transgenic, Signal Transduction, Amyloid beta-Peptides, Microglia, MicroRNAs, Mice, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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